Establishment of a tTA-dependent photoactivatable Cre recombinase knock-in mouse model for optogenetic genome engineering

Tomoka Takao, Yuichi Hiraoka, Kenji Kawabe, Daisuke Yamada, Lu Ming, Kohichi Tanaka, Moritoshi Sato, Takeshi Takarada

Research output: Contribution to journalArticle

Abstract

The Cre-loxP recombination system is widely used to generate genetically modified mice for biomedical research. Recently, a highly efficient photoactivatable Cre (PA-Cre) based on reassembly of split Cre fragments has been established. This technology enables efficient DNA recombination that is activated upon blue light illumination with spatiotemporal precision. In this study, we generated a tTA-dependent photoactivatable Cre-loxP recombinase knock-in mouse model (TRE-PA-Cre mice) using a CRISPR/Cas9 system. These mice were crossed with ROSA26-tdTomato mice (Cre reporter mouse) to visualize DNA recombination as marked by tdTomato expression. We demonstrated that external noninvasive LED blue light illumination allows efficient DNA recombination in the liver of TRE-PA-Cre:ROSA26-tdTomato mice transfected with tTA expression vectors using hydrodynamic tail vein injection. The TRE-PA-Cre mouse established here promises to be useful for optogenetic genome engineering in a noninvasive, spatiotemporal, and cell-type specific manner in vivo.

Original languageEnglish
Pages (from-to)213-217
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume526
Issue number1
DOIs
Publication statusPublished - May 21 2020

Keywords

  • Cre recombinase
  • Photoactivatable
  • Tetracycline-controlled gene induction

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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